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Carl-Erik Dempfle

Publications and source records attributed to Carl-Erik Dempfle.

At least 19 recordsLinked to original sources
PubMed2007

[Clinical assessment of potential fields of application of recombinant factor VIIa in internal and pediatric diseases. Recommendations of an expert group].

Recombinant factor VIIa (rFVIIa) is increasingly used outside the labeled indications for treatment of life-threatening bleeding episodes after failure of the respective standard therapy. An interdisciplinary group of experts summarizes the state of knowledge of the use of rFVIIa in gastroenterology and hepatology, thrombocytopenia and -pathia, coagulation factor deficiencies, von Willebrand's disease, periinterventional bleeding without specific bleeding diathesis, drug-induced bleeding, disseminated intravascular coagulation, and neonatology. The most commonly used dose is 90 microg/kg body weight rFVIIa as bolus, if necessary followed by additional injections at intervals of 2-3 h. In factor VII deficiency lower dosages of 15-30 microg/kg body weight of rFVIIa are given every 4-6 h, whereas higher doses of 150-200 microg/kg body weight are used in neonates.

Adult↗
PubMed2006

Performance evaluation of a new rapid quantitative assay system for measurement of D-dimer in plasma and whole blood: PATHFAST D-dimer.

D-dimer is an indicator for in vivo fibrin formation, reflecting the formation of fibrin crosslinked by factor XIIIa. D-dimer assays are frequently used in emergency situations, such as diagnosis of venous thrombosis and pulmonary embolism, or disseminated intravascular coagulation. In these conditions, short sample turnaround times are essential. The PATHFAST D-dimer assay allows rapid quantitative measurement of D-dimer in plasma and whole blood. The study shows an excellent correlation between whole blood and plasma measurement of D-dimer both in the high range, as well as in the normal range. Intra-assay and inter-assay coefficients of variation (CV) were below 10%. The upper limit of normal (ULN = mean value measured in 100 samples from healthy blood donors + 2 x S.D.) was approximately 1 microg/ml FEU, using the assay-specific calibration. The maximal value measured in 20 replicates of calibrator 1 containing no D-dimer antigen was 0.00052 microg/ml FEU, and this 10-fold lower than the declared detection limit of 0.005 microg/ml FEU. In conclusion, the PATHFAST D-dimer assay is the first automated fully quantitative D-dimer assay, which can use plasma and whole blood as sample materials in parallel.

Blood↗
PubMed2006

Molecular and clinical spectrum of type I plasminogen deficiency: A series of 50 patients.

Severe type I plasminogen (PLG) deficiency has been causally linked to a rare chronic inflammatory disease of the mucous membranes that may be life threatening. Here we report clinical manifestations, PLG plasma levels, and molecular genetic status of the PLG gene of 50 patients. The most common clinical manifestations among these patients were ligneous conjunctivitis (80%) and ligneous gingivitis (34%), followed by less common manifestations such as ligneous vaginitis (8%), and involvement of the respiratory tract (16%), the ears (14%), or the gastrointestinal tract (2%). Four patients showed congenital occlusive hydrocephalus, 2 with Dandy-Walker malformation of cerebellum. Venous thrombosis was not observed. In all patients, plasma PLG levels were markedly reduced. In 38 patients, distinct mutations in the PLG gene were identified. The most common genetic alteration was a K19E mutation found in 34% of patients. Transient in vitro expression of PLG mutants R134K, delK212, R216H, P285T, P285A, T319_N320insN, and R776H in transfected COS-7 cells revealed significantly impaired secretion and increased degradation of PLG. These results demonstrate impaired secretion of mutant PLG proteins as a common molecular pathomechanism in type I PLG deficiency.

Animals↗
PubMed2006

Activation of coagulation during alimentary lipemia under real-life conditions.

High intake of saturated fat is a predictor of coronary heart disease mortality. The phenomenon of postprandial angina pectoris has been described many years ago. Although earlier studies have demonstrated postprandial activation of coagulation factors VII and XII, platelets and monocytes, conclusive evidence for intravascular fibrin formation after a fat-rich meal has not been reported yet. The present study included 33 healthy physicians (7 females, 26 males) with a mean age of 42 years (range 27-62 years), and 27 coronary heart disease patients (8 females, 19 males) with a mean age of 63 years (range 47-81 years). Of the coronary heart disease patients, 26/27 were treated with acetylsalicylic acid and 25/27 with lipid-lowering drugs simvastatin or atorvastatin. Blood samples were drawn 30-60 min before and 30-60 min after a dinner consisting of rye bread with liversausage and black pudding as hors d'oeuvre, lettuce with smoked bacon in a lard dressing, stuffed fried goose with red cabbage, potato dumplings and sweet chestnuts, and white and brown mousse au chocolat. Average intake per person was 3760 kcal, with 125.9 g protein, 238.0 g fat and 268.9 g carbohydrate. We measured a significant postprandial increase in fibrinopeptide A (FpA) levels from 1.14+/-1.23 microg/l to 4.18+/-2.86 microg/l (p<0.0001) in healthy probands, and 4.66+/-13.61 microg/l to 12.80+/-15.04 microg/l (p<0.0001) in coronary heart disease patients. Triglycerides increased from 137.6+/-60.5 to 201.5+/-75.0 mg/dl in healthy probands and from 211.9+/-94.6 to 273.6+/-122.5 mg/dl in coronary heart disease patients. Fat-rich meals may cause procoagulant episodes, which may promote vascular complications such as myocardial infarction, transient ischemia attacks in susceptible persons.

Adult↗
PubMed2006

New disseminated intravascular coagulation score: A useful tool to predict mortality in comparison with Acute Physiology and Chronic Health Evaluation II and Logistic Organ Dysfunction scores.

OBJECTIVE: To compare the performance of a coagulation score-the new scoring system for diagnosing disseminated intravascular coagulation (DIC)-with the Acute Physiology and Chronic Health Evaluation (APACHE) II and Logistic Organ Dysfunction score in mortality prediction. DESIGN: Single-center retrospective study. SETTING: Medical intensive care unit of the University of Munich. PATIENTS: A total of 797 patients admitted to the intensive care unit between January 1, 1996, and January 1, 2001. METHODS: A retrospective analysis of all patients was done if the coagulation variables d-dimer, platelet count, fibrinogen, and prothrombin index were available within the first 12 hrs after admission. Patients with missing values, fibrinolytic therapy, or unknown survival status were excluded from analysis. As a marker of fibrin generation, d-dimer was measured and integrated into the scoring system for DIC together with prothrombin time, fibrinogen, and platelet count. A coagulation score was calculated in analogy with the scoring system for DIC in patients not typically developing DIC. MEASUREMENTS AND RESULTS: Overall, the mean result of the scoring system for DIC was 2.2 points. An increasing scoring system for DIC was associated with increasing mortality in patients with serious infections. Use of the scoring system for DIC in addition to the APACHE II score helps to predict mortality better than the APACHE II score alone, especially in patients with infections. The Cox regression analysis showed that the DIC and APACHE II scores correlated independently with survival time with a greater effect of the DIC score than the APACHE II or the Logistic Organ Dysfunction score. Similar results were obtained using the coagulation score in patients with cardiocirculatory diseases. CONCLUSION: Our retrospective data suggest that a combination of the APACHE II score and the scoring system for DIC predicts mortality in critically ill patients with available variables better than the APACHE II score alone. This effect is most pronounced among patients with active infection. These results of our retrospective analysis have to be confirmed in a prospective study.

APACHE↗
PubMed2006

Valproate-associated coagulopathies are frequent and variable in children.

PURPOSE: Valproic acid (VPA) is an antiepileptic drug (AED) commonly used for generalized and focal epilepsies. The clinical relevance of coagulopathies, known as side effects of VPA therapy, especially thrombocytopenia, von Willebrand disease, and a decrease of factor XIII, is still unclear. METHODS: In our institute, we noticed a high incidence of clinically relevant coagulation problems related to VPA in eight patients within 1 year only and a further seven children with significant coagulopathy were identified in the context of planned surgery. RESULTS: We provide an overview of these patients and all six VPA-induced coagulopathies. CONCLUSIONS: At this time, it cannot be recommended to control all hemostatic parameters in every patient. Whenever an increased bleeding tendency is observed, or before surgical procedures, a platelet count, thrombelastography, prothrombin time, activated partial thromboplastin time, TT, fibrinogen, von Willebrand factor, and factor XIII should be examined. With 385 VPA-treated patients per year and 15 cases of coagulation disorders in this period, we estimate the incidence of coagulation disorders related to VPA in children to be nearly 4%.

Age Factors↗
PubMed2006

Sensitivity and specificity of a quantitative point of care D-dimer assay using heparinized whole blood, in patients with clinically suspected deep vein thrombosis.

D-dimer assays are efficient in the exclusion diagnostics of deep vein thrombosis (DVT) in patients without severe concomitant diseases. We have determined diagnostic sensitivity and specificity of a new point-of-care rapid assay for quantitative determination of D-dimer in heparinized whole blood in outpatients with suspected DVT. In 19 participating centers, 637 patients were included in the study, of which 77 were excluded, the majority because of inadequate documentation of analytical quality control measures. DVT was diagnosed in 223 of the remaining 560 patients by duplex ultrasound examination. The POC D-dimer assay showed a high sensitivity of 96.9% for the diagnosis of DVT and a high specificity of 60.8% at a pre-specified cutoff of 0.5 microg/ml. For Tina-quant D-dimer, sensitivity was slightly lower at 94.9%, with a specificity of 64.8%. The VIDAS D-dimer assay showed a sensitivity of 98.2%, but specificity was 40.7%. The area under the curve (AUC +/- standard error, 95% confidence interval) was 0.879 +/- 0.019 (0.845-0.909) for POC D-dimer, 0.908 +/- 0.016 (0.877-0.934) for Tina-quant D-dimer, and 0.895 +/- 0.018 (0.862-0.922) forVIDAS D-dimer. Differences were not statistically significant. The new whole blood POC D-dimer assay is a reliable tool for exclusion of DVT in symptomatic outpatients, displaying a comparable diagnostic performance as VIDAS D-dimer and Tina-quant D-dimer assays.

Adolescent↗
PubMed2005

Evaluation of the automated coagulation analyzer Sysmex CA-7000.

INTRODUCTION: Centralization of laboratory diagnostics and an increasing number of urgent requests and nonstandard samples raise the need for short turn-around times and high-throughput analyzers for coagulation tests. The aim of the present study was to evaluate the analytical and technical performance of the Sysmex CA-7000 coagulation analyzer under routine laboratory conditions. MATERIALS AND METHODS: We evaluated the Sysmex CA-7000 in comparison to the Sysmex CA-6000 analyzer for PT, INR, aPTT, Clauss, and derived fibrinogen. We also compared antithrombin (AT) measured on the Sysmex CA-7000 and Dimension RxL. Imprecision studies were performed, and throughput, online, and STAT functions and the handling of routine samples were evaluated. RESULTS: The Sysmex CA-7000 showed very low intra-assay and interassay variability for all parameters. The method comparison study showed good comparability to the Sysmex CA-6000 and Dimension RxL. The throughput of the Sysmex CA-7000 was 2.5--3 times faster than that of Sysmex CA-6000. No interference was seen for total bilirubin up to 710 micromol/L. Triglyceride levels >11.4 mmol/L resulted in invalid PT measurements and levels >3.42 mmol/L gave invalid results for Clauss fibrinogen on the CA-7000 analyzer. CONCLUSIONS: This is the first published evaluation of the analytical and technical performance of the coagulation analyzer Sysmex CA-7000. We conclude that the CA-7000 is well suited for coagulation laboratories with high sample throughput and a high number of nonstandard samples.

Antithrombin III↗
PubMed2005

Influence of receptor activator of nuclear factor kappa B on human aortic valve myofibroblasts.

Calcific aortic valve stenosis, the main heart valve disease in the elderly, is based on progressive calcification and fibrous thickening of the valve. Several reports addressed the pathogenesis of tissue calcification in this disorder, but few data exist on the molecular mechanisms of the fibrosis and remodeling of the extracellular matrix. The cytokine "receptor activator of nuclear factor kappa B ligand" (RANKL), is expressed in stenotic aortic valves and involved in valvular calcification during calcific aortic valve stenosis. The present study aimed to assess the influence of RANKL on the molecular mechanisms of connective tissue remodeling. In an established cell culture model of primary human aortic valve myofibroblasts, stimulation with RANKL increased cell proliferation as compared to medium alone. Matrix metalloproteinase (MMP)-1 was detectable time-dependently in conditioned media from RANKL-stimulated cells, but absent in media from control cells. MMP-1 activity was increased by RANKL, as measured by collagenase activity assay. Zymography showed an increase in active MMP-2 in RANKL-stimulated cells. These results support the concept that MMPs are involved in the connective tissue remodeling during calcific aortic valve stenosis. RANKL might regulate this process by promoting cell proliferation and MMP expression and activation.

Aortic Valve↗
PubMed2005

Validation, calibration, and specificity of quantitative D-dimer assays.

Assays for D-dimer antigen are based on monoclonal antibodies reactive with epitopes found on fibrin fragment D-dimer but not on fibrinogen fragment D, other fibrinogen degradation products, or native fibrinogen. The antibodies react with conformational epitopes generated by factor XIII-induced linkage of the C-terminal appendages of the fibrin gamma-chains of adjacent D-domains within a fibrin polymer. For some monoclonal antibodies, degradation of the cross-linked fibrin compound by plasmin is an additional requirement for the generation of the epitope. In clinical plasma samples, D-dimer antigen assays detect an array of fibrin compounds of different molecular weights, including fibrin fragment D-dimer as well as higher-molecular-weight fibrin degradation products and fibrin X-oligomers. Most D-dimer antigen represents cross-linked soluble fibrin present in circulation rather than degradation products from particulate clots. Due to differences in epitope reactivity, harmonization of D-dimer antigen assays can only be achieved with standard preparations containing a similar variety of cross-linked fibrin compounds. Assay technologies include manual latex agglutination assays, automated latex-enhanced light-scattering immunoassays, enzyme-linked immunoassays, and others.

Antibodies, Monoclonal↗
PubMed2004

Disseminated intravascular coagulation and coagulation disorders.

PURPOSE OF REVIEW: An update on recent developments in diagnosis and treatment of disseminated intravascular coagulation. RECENT FINDINGS: Disseminated intravascular coagulation is defined as a typical disease condition with laboratory findings indicating massive coagulation activation and reduction in procoagulant capacity. Clinical syndromes associated with the condition are consumption coagulopathy, sepsis-induced purpura fulminans, and viral hemorrhagic fevers. Consumption coagulopathy is observed in patients with sepsis, aortic aneurysms, acute promyelocytic leukemia, and other disseminated malignancies. Sepsis-induced purpura fulminans is characterized by microvascular occlusion causing hemorrhagic necrosis of the skin and organ failure. Viral hemorrhagic fevers result in massively increased tissue factor production in monocytes and macrophages, inducing microvascular thrombosis and consumption of platelets and coagulation factors. Current scoring systems do not distinguish between patients with asymptomatic disseminated intravascular coagulation, consumption coagulopathy and thrombotic syndromes. Patients with sepsis may be identified by activated partial thromboplastin time waveform analysis performed as part of routine coagulation testing. Drotrecogin alpha (activated) reduces mortality in patients with severe sepsis with and without disseminated intravascular coagulation and has been used in patients with sepsis-induced purpura fulminans. Tifacogin does not reduce mortality in severe sepsis associated with impaired coagulation. Patients with heterozygous factor V Leiden mutation and severe sepsis showed a lower 28-day mortality than patients without this mutation, supporting the assumption that an enhanced level of coagulation activation may be beneficial in patients with severe sepsis. SUMMARY: Whereas antithrombin and tifacogin failed to improve clinical outcome in severe sepsis, drotrecogin alpha (activated) increased the chances of survival of patients with severe sepsis with and without disseminated intravascular coagulation.

Journal Article↗
PubMed2004

Factor XIII deficiency associated with valproate treatment.

PURPOSE: We present two children who developed a deficiency of factor XIII with valproate (VPA) treatment. This coagulation disorder has not been described in association with VPA treatment in children, and only very recently in one adult patient. RESULTS: Both patients showed recurrent epistaxis as major clinical sign of a combination of decreased coagulation parameters (factor XIII deficiency with thrombocytopenia and decreased von Willebrand factor, respectively). A few days after reduction or withdrawal of VPA treatment, clinical symptoms disappeared, and laboratory findings were within normal range. CONCLUSIONS: VPA is known to influence the synthetic function of the liver and the number and function of megakaryocytes. Therefore an alteration of the factor XIII level by VPA is conceivable. Our case reports suggest that bleeding symptoms during VPA treatment may be caused or aggravated by a decreased factor XIII activity. A determination of factor XIII activity should be considered before surgical procedures during VPA treatment to minimize the risk of (severe) postsurgical bleeding complications.

Anticonvulsants↗